title: The pharmacokinetics of PF-734200, a DPP-IV inhibitor, in subjects with renal insufficiency.
abstract: OBJECTIVE
  PF-734200 is a potent, selective inhibitor of DPP-IV. This two-part study evaluated the pharmacokinetics (PK) of oral 20mg PF-734200 in subjects with varying degrees of renal insufficiency or with end-stage renal disease (ESRD) requiring chronic haemodialysis (HD). The study also assessed the HD clearance of PF-734200 in ESRD.
  
  
  METHODS
  Part 1 included subjects with normal renal function or renal insufficiency but not on HD. Subjects received a single dose of 20mg PF-734200 while fasting and serum and urine samples were collected. In part 2, period 1, 1h after HD, a single 20-mg dose was given to subjects with ESRD and serum samples were collected. After a 7-day washout, subjects received another dose followed by collection of serum samples (period 2), during which HD was initiated 4h after dosing. Dialysate samples were collected to quantify amount of drug removed, from which HD clearance was calculated. The fraction of drug dialysed was calculated using an AUC-based method.
  
  
  RESULTS
  Systemic exposures of PF-734200 increased approximately 1.5-, 2.2-, 2.1- and 2.8-fold in subjects with mild, moderate, or severe renal insufficiency or ESRD, respectively, compared with subjects with normal renal function. The terminal half-life increased from 16.2h in subjects with normal renal function to 36.6h in subjects with ESRD. Approximately, 29% of PF-734200 in the body after a single-dose administration was dialysed by 4h HD.
  
  
  CONCLUSIONS
  Systemic exposure of PF-734200 increases with decreasing renal function. The effect of HD on drug removal is modest.
authors.affiliation: Pfizer Global Research and Development, New London, CT Orlando Clinical Research, Orlando, FL, USA. haiqing.dai@pfizer.com
authors.forename: Haiqing
authors.initials: H
authors.lastname: Dai
authors.forename: Susan L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Steven G
authors.initials: SG
authors.lastname: Terra
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.forename: William B
authors.initials: WB
authors.lastname: Smith
authors.forename: Harry
authors.initials: H
authors.lastname: Alcorn
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Boyd
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Tu T
authors.initials: TT
authors.lastname: Nguyen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000188:drug therapy / Q000378:metabolism*; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011743:Pyrimidines; D011759:Pyrrolidines; C558848:gosogliptin